Hopkins Clinical Center for Pulmonary Vascular Disease Phenomics Program

项目概述：霍普金斯临床中心肺血管疾病表型组学项目霍普金斯肺高血压（PH）项目由来自不同机构部门和部门的高度敬业的多学科专家组组成，他们在当前和以前nih支持的研究项目框架内有着悠久的密切互动和丰富的生产力。我们的项目主要提供PH世界分类的所有五组患者的综合管理，并且也有参与行业赞助以及nih赞助的PH治疗的多中心临床试验的悠久历史。由于右心室（RV）功能是PH患者死亡的主要决定因素，我们建议对PH患者进行彻底的表型分析，主要关注右心室和肺血管（PV）以及RV-PV解耦之间的复杂关系，目的是进一步研究它们对PH发病率和死亡率的关键影响。利用我们在PH方面广泛的临床知识以及我们在分子和诊断肺部医学和心脏病学方面的专业知识，我们建议使用1)超声心动图和心脏磁共振成像（cMRI）来确定心室功能的无创测量方法及其预测预后的能力；2)有创血流动力学评估RV/PV相互作用对深层表型和生存的影响；3)分子（基因组学、遗传学和血清生物标志物）内表型分型。在此应用中提出的临床、血流动力学、成像、血清和遗传生物标志物的搜索可以很容易地应用于PVDOMICs作为相关变量的所有临床中心

DESCRIPTION (provided by applicant): Project Summary: Hopkins Clinical Center for Pulmonary Vascular Disease Phenomics Program The Hopkins Pulmonary Hypertension (PH) program is composed of a highly dedicated, multi-disciplinary group of experts from various institutional divisions and departments, who have a long history of close interaction and rich productivity within the framework of current and previous NIH-supported research projects. Our Program primarily provides comprehensive management of patients from all five groups of the PH World Classification, and also has a long history of participation in industry-sponsored as well as NIH-sponsored multicenter clinical trials for PH treatment. Since right ventricular (RV) function is the main determinant of death in PH, we propose thorough phenotyping of PH patients with a primary focus on the complex relationship between the RV and the pulmonary vasculature (PV) and RV-PV uncoupling, with the goal to further examine their crucial impact on morbidity and mortality in PH. Leveraging our extensive clinical knowledge in PH and our expertise in molecular and diagnostic pulmonary medicine and cardiology, we propose to use 1) echocardiography and cardiac magnetic resonance imaging (cMRI) to identify non-invasive measures of RV performance and their capacity to predict outcomes; 2) invasive hemodynamic assessment of RV/PV interaction for its impact on deep phenotyping and survival; and 3) molecular (genomics, genetics, and serum biomarkers) for endophenotyping. The search for clinical, hemodynamic, imaging, serum and genetic biomarkers proposed in this application can be readily applied to all clinical centers in the context of the PVDOMICs as relevant variables for disease risk assessment, dynamic phenotyping (baseline and in response to treatment), endophenotyping, and as intermediate or primary outcomes in clinical trials. In summary, while the choice of parameters, studies and target populations will be left to the discretion of the DCC, our PH clinical center will offer the unique expertise of a multidisciplinary and highly integrated team of experts in this new endeavor to redefine PH phenotypes from all five groups of PH, thus ensuring success of the PVDOMICs efforts.